Terry Orr-Weaver (Whitehead Institute, MIT)
MolBio Seminar Series
Terry L. Orr-Weaver is an American Cancer Society Research Professor in the Department of Biology at the Massachusetts Institute of Technology and a Member of the Whitehead Institute for Biomedical Research. She obtained her BA degree in Chemistry, summa cum laude, from the University of California, San Diego, in 1977 and her PhD in the laboratory of Dr. Jack Szostak in Biological Chemistry from Harvard University in 1984. Following postdoctoral training in developmental biology in Dr. Allan Spradling’s laboratory at the Department of Embryology of the Carnegie Institution of Washington in Baltimore, MD, she joined MIT as an Assistant Professor of Biology and an Associate Member of the Whitehead Institute in 1987. Her research addresses regulation of cell division during development, and her laboratory has discovered crucial control proteins for chromosome segregation and DNA replication. From 2004-2006 she was Vice-President, President, and Past-President of the Genetics Society of America. She was Vice-Chair and Chair of the Scientific Advisory Committee of the Damon Runyon Cancer Research Foundation from 2002-2006. She was President of the National Drosophila Board of Directors 2009-2010 and served the board as Past President until 2013. In addition, she is chair of the Scientific Advisory Committee of Children’s Hospital in Boston. In 2006 she was elected a fellow of the American Academy of Microbiology and a member of the National Academy of Sciences. In 2010 she was elected a fellow of the American Association for the Advancement of Science. She received the FASEB Excellence in Science award in 2013.
Post-Transcriptional Regulation of the Oocyte-to-Embryo Transition
The transition from the differentiated oocyte to the totipotent embryo marks the onset of development. This occurs in the absence of transcription, and thus must be regulated by post-transcriptional control mechanisms such as translation and protein turnover. We are investigating the regulation of the oocyte-to-embryo transition in Drosophila, in which egg activation can be experimentally separated from fertilization and zygotic gene expression. To define the developmental parameters of this transition as well as the cell cycle change from meiosis to mitosis, we combined genome-wide polysome profiling and ribosome footprinting to survey the translational status of thousands of mRNAs and integrated those results with quantitative mass spectrometry measurements of proteome remodeling. Genome-wide translational analysis demonstrated extensive translational changes with hundreds of translationally inhibited or activated mRNAs. Importantly, we show that PNG kinase, previously known to promote translation of Cyclin B and Smaug, acts as a major regulator of the oocyte-to-embryo transition by controlling the translational levels of at least 60% of translationally controlled mRNAs. Integrating proteome- and translation-based approaches revealed that translational upregulation is largely responsible for protein increases, but that only a small fraction of the translationally upregulated mRNAs cause an increase in the abundance of the corresponding protein. We demonstrate that protein degradation, regulated in part by a meiosis-specific form of the Anaphase Promoting Complex (APC), is necessary for the change from meiosis in the oocyte to mitosis in the embryo. One key target is the Polo kinase inhibitor Matrimony, whose levels must be reduced for proper embryogenesis. The proteomics and translatome studies also indicate an unexpected compensatory dynamic between translation and protein turnover during the return to totipotency.
Free and open to the university community and the public